OBJECTIVES: To determine the lifetime costs and morbidity associated with nonadherence to lipid-lowering and antihypertensive therapy in a population of hypertensive patients with additional cardiovascular risk factors. METHODS: A Markov model was constructed to assess the lifetime costs and outcomes associated with different levels of adherence to lipid-lowering and antihypertensive therapy in a cohort of patients aged 40 to 79 years. Three adherence scenarios were considered: no treatment, typical adherence, and ideal adherence. Patient characteristics were modeled on those of participants in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA); event probabilities for coronary heart disease and stroke were estimated using risk prediction algorithms from the Framingham Heart Study. The ideal adherence scenario modeled the experience of ASCOT-LLA patients, with adherence levels based on those observed in the trial. The typical adherence scenario employed real-world adherence rates and annual transitions based on prescription records from the California Medicaid system. Risk reductions for the various adherence states in this scenario were drawn from clinical trials. Model outputs included frequencies of primary and secondary heart disease and stroke, life expectancy, and pharmacy-related and event-specific costs in 2006 USD. RESULTS: The mean number of events per patient was 0.738 in the no treatment scenario, 0.610 for typical adherence, and 0.441 for ideal adherence. Mean life expectancy was 14.73 years for no treatment, 15.07 years for typical adherence, and 15.49 for ideal adherence. The incremental cost effectiveness ratio per life-year gained was $30,585 between typical adherence and no treatment, and $22,121 between ideal adherence and typical adherence. CONCLUSION: Nonadherence to lipid-lowering and antihypertensive therapy contributes significantly to the clinical and economic burden of heart disease and stroke in the population considered. Patients with typical adherence levels receive approximately 50% of the risk reduction seen in clinical trials with controlled levels of ideal adherence.